• Proceedings of the PSK Conference
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• 2002.10a
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• pp.169-170
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• 2002

It has been well known for the stereoselectivity in pharmacodynamic effects of many xenobiotics including therapeutic agents, which have lead to the development of enantiomer drugs. Compared to pharmacodynamic stereoselectivity, stereoselective pharmacokinetics of each enantiomer has not been seriously considered in the development of enantiomer drugs although many reports have been demonstrated the stereoselective absorption and metabolism of racemic drug (e.g verapamil). (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.282.2-283
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• 2003

The carboxylated acidic non-steroidal antiinflammatory drugs (NSAIDs) constitute the principal class of agents for controlling the pain and inflammation of the rheumatic diseases. It is mostly administered as a racemic mixture like most other drugs with asymmetric carbon atoms. However enantiomers of many racemic drug substances have been shown to posses different pharmacological toxicological properties. (omitted)

• Biotechnology and Bioprocess Engineering:BBE
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• v.8 no.1
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• pp.1-8
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• 2003

With current developments in enzyme-catalyzed reactions and techniques available for rational redesign of natural biocatalysts, the enzymatic biosynthesis can become one of the most valuable Synthetic methods. Enzymatic regioselective catalysis in organic media has played a key role in pursuing asymmetric synthesis for active chiral compounds. Here, we shortly do-scribe some historical issues of the rapidly growing area, enzymatic catalysis in synthetic organic chemistry and then review researches that have been carried out in the regioselective enzymatic catalysis for the past two decades. An application of this technology to the modification of some potential target drug co m pound will be adios presented.

• Journal of the Korean Chemical Society
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• v.59 no.6
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• pp.488-492
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• 2015

In this study, the effective preparation method of (S)-(+)-pranidipine, the active component of antihypertensive drug as a calcium channel blocker, was developed using optical resolution. The racemic monocarboxylic acid 5 obtained by the hydrolysis of (±)-pranidipine was mixed with optically active quinidine to form salts, and the insoluble diastereomeric salt was collected and successive treatment with base and acid furnished (R)-(-)-carboxylic acid 7. (S)-(+)-Pranidipine was prepared by esterification of this acid with cinnamyl alcohol, and the analysis by chiral HPLC showed 100% enantiomeric excess (ee). This process would be industrially very useful to prepare chiral (S)-(+)-pranidipine, since the use of strong base and anhydrous solvents, and ultra-low temperature condition were excluded in this process.

• Analytical Science and Technology
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• v.33 no.2
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• pp.59-67
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• 2020

Nadolol is a β-blocker drug, which effectively manages hypertension and angina pectoris. Its chemical structure allows the formation of four possible stereoisomers. A coupled column high-performance liquid chromatographic (HPLC) system with UV and fluorescence detection was investigated for simultaneously determining four nadolol enantiomers in human plasma. The plasma samples were prepared using a convenient liquid-liquid extraction process and passed through HPLC. Nadolol was initially separated from the endogenous compounds or other impurities in human plasma on a Phenomenex silica column, and its enantiomers were resolved and determined on a Chirapak AD-H column. The developed HPLC method achieved an effective chiral separation and significantly eliminated endogenous compound interference. This optimal HPLC method was validated following FDA guidelines. The results showed good selectivity, linearity, accuracy (90.50 % - 105.27 %), and precision (RSDs < 9.52 %) for each enantiomer. This method was also successfully applied to determine nadolol enantiomers in the plasma samples of a healthy male volunteer (after orally administering 80 mg racemic nadolol), proving its suitability for nadolol stereoselective pharmacokinetic studies.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.34-35
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• 1993

The Development of new asymmetric induction methods useful for syntheses of biologically active natural products and drugs, using C4-chiral 1,3-th-iazolidine-2-thiones, has been a recent focus of interest. 1-8) The present account describes the significance of particular heterocycles in the synthetic development of new 1${\beta}$-substituted carbapenems. A fungal metabolite, (＋)-thienamycin (1) has attracted one's attention as a hopeful candidate for new-generation antibiotic drugs because of its strong antimicrobial activities and wide antimicrobial spectra due to the extensive inhibition against various ${\beta}$-lactamases. However, it has been serious problems toward a practically useful drug that (＋)-thienamycin is fairly labile in the solution and can be metabolized by renal dehydropept- idase-I (DHP-I). Recently, a Merck Sharp ＆ Dohme research group exploited a non-natural ${\beta}$-lactam, imipenem (2) which has been appeared in the drug market as the first carbapenem-type antibiotic drug. 9) However 2 must be used with a DHP-I inhibitor, cilastatin sodium (3).9) Thus, a 1,${\beta}$-methyl- carbapenem derivative 4 has been disclosed by the same group. 10) It seems to be more hopeful candidate as a new-generation antibiotic because it can directly resist against metabolism by the renal DHP-1 without an enzyme inhibitor 3. 10)

• Mass Spectrometry Letters
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• v.2 no.4
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• pp.88-91
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• 2011

The pharmacokinetic properties of S-amlodipine were studied using racemic amlodipine and single S-enantiomer (SK310) administration to rats. Plasma levels of the drug were determined using chiral liquid chromatography coupled with tandem mass spectrometry following solid phase extraction. The stereospecific analysis of amlodipine was performed on an ${\alpha}$-acid glycoprotein (AGP) column using a mobile phase comprising 10 mM ammonium acetate (pH 4.0) and propanol at a flow rate of 0.2 mL/min. This method was used to perform a comparative study of the pharmacokinetics of amlodipine and SK310. The results revealed that the pharmacokinetic profile of S-amlodipine after the administration of SK310 was comparable to that following the administration of the racemic mixture.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.182.3-183
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• 2003

(-)-Antofine is phenanthroindolizidine alkaloid being isolated from Cynanchum vincetoxicum. It has powerful cytotoxicity toward drug-sensitive KB-3-1 and multidrug resistant KB-V1 cancer cell line. We have successfully accomplished stereoselective total synthesis by using palladium catalyzed Stille coupling of l0-bromomethyl-2,3 ,6-trimethoxy-phenanthrene and (R)-(E)-4-(tributylstannanyl)but-3-en-2-o1, Overmann rearrangement of imidate, and RCM(ring-closing metathesis) for construction of pyrrolidine.

• Bulletin of the Korean Chemical Society
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• v.31 no.6
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• pp.1496-1500
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• 2010

Sibutramine enantiomers were separated successfully by capillary zone electrophoresis using substituted cyclodextrins as chiral selectors. The effects of cyclodextrin concentration, pH, voltage, buffer type, and electrolyte concentration on the migration time and resolution of enantiomers were examined. Separation of sibutramine enantiomers on an unmodified fused silica capillary (total length, 54 cm; effective length, 45 cm) was achieved using a mixed buffer of 20 mM phosphate/10 mM citrate containing either 5 mM methyl-${\beta}$-cyclodextrin (pH 4.3) or 5 mM carboxymethyl-${\beta}$-cyclodextrin (pH 6.5). Samples were injected with a pressure of 50 mbar for 5 s and were detected at a wavelength of 223 nm. The established method showed good precision and accuracy, with intra- and inter-day variations of less than 2.9 and 4.7%, respectively, and recoveries of 95.7 - 103.8%. The stability constants of (R)- and (S)-sibutramine demonstrated that the resolution of sibutramine enantiomers was attributable primarily to the difference in stability constants. When this optimized method was applied to the determination of sibutramine enantiomers in commercial drug formulations, it proved to be economical and convenient, affording sufficient accuracy, precision, and reproducibility as well as sensitivity and selectivity.

• Microbiology and Biotechnology Letters
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• v.37 no.2
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• pp.118-124
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• 2009

Esterase EM2L8 gene isolated from deep sea sediment was expressed in Escherichia coli BL21 (DE3) and the esterase activity of the cell-free extract was assayed using p-nitrophenyl butyrate-spectrophotometric method. Its optimum temperature was $40-45^{\circ}C$ and 45% activity of the maximum activity was retained at $15^{\circ}C$. The activation energy at $15-45^{\circ}C$ was calculated to be 4.9 kcal/mol showing that esterase EM2L8 was a typical cold-adapted enzyme. Enzyme activity was maintained for 6 h and 4 weeks at $30^{\circ}C$ and $4^{\circ}C$, respectively. When each ethanol, methanol, and acetone was added to the reaction mixture to 15% concentration, enzyme activity was maintained. In the case of DMSO, enzyme activity was kept up to 40% concentration. (S)-4-Chloro-3-hydroxy butyric acid is a chiral intermediate for the synthesis of Atorvastatin, a hyperlipemia drug. When esterase EM2L8 (40 U) was added to buffer solution (1.2 mL, pH 9.0) containing ethyl-(R,S)-4-chloro-3-hydroxybutyrate (38 mM), it was hydrolyzed into 4-chloro-3-hydroxy butyric acid with a rate of $6.8\;{\mu}mole/h$. The enzyme hydrolyzed (S)-substrate more rapidly than (R)-substrate. When conversion yield was 80%, e.e.s value was 40%. When DMSO was added, hydrolysis rate increased to $10.4\;{\mu}mole/h$. The plots of conversion yield vs e.e.s in the presence or absence of DMSO were almost same, implying that the reaction enantioselectivity was not changed by the addition of DMSO. Taken together, esterase EM2L8 had high activity and stability at low temperatures as well as in various organic solvents/aqueous solutions. These properties suggested that it could be used as a biocatalyst in the synthesis of useful pharmaceuticals.